The studies outlined in this proposal will focus on cyclin D1, a key cell cycle control protein that is one of the most prevalent oncogenes in human cancers. Studies from this laboratory have identified cyclin D1 as an important mediator of hepatocyte proliferation in the regenerating liver. However, the biochemical and cellular functions of cyclin D1 have not been fully characterized despite extensive study. The purpose of these studies is to characterize a novel effect of cyclin D1 in hepatocytes. Based on preliminary evidence, the primary hypothesis is that cyclin D1 regulates sex steroid hormone metabolism and signaling at the cellular and tissue level, and that these effects play a biologically significant role in the liver. It is also hypothesized that the C-terminus of cyclin D1 plays an important role in modulating sex steroid signaling as well as other biologically relevant effects in the liver. Additional studies will identify novel cyclin D1 binding partners. Identification of novel roles for cyclin D1 in the liver are expected to increase our understanding of an important liver oncogene.